Normal cell membrane function is essential for living organisms. Cell fusion is a measure of plasma membrane activity, and occurs spontaneously in vivo, e.g., during fertilization and the formation of mature muscle cells. We propose to analyze a series of somatic cell line variants (putative mutants) which are either altered in cell fusion capability or altered in their reaction to cytotoxic drugs known to suppress both cell fusion and endocytosis. Analyses should reveal the interrelationship of cell structure and membrane function. Essential steps in the process of plasma membrane fusion may also be revealed. This series of mutants should help define the genetic control of essential steps in plasma membrane function during cell fusion. In addition, because of the natural relationship between all plasma membrane fusion processes, these mutants may also help describe basic functional steps in endocytosis. An understanding of the genetics of membrane activity is of basic importance in understanding the biology of all higher organisms.